Nuclear Science Advisory Committee Isotopes Subcommittee

Co-chairs Ani Aprahamian Donald Geesaman A Strategic Plan for the Isotope Development and Production for Research and Applications Program

Presentation to NSAC 27 July 2009 Report Status and Versions

July 20, 2009 18 July version sent to NSAC Still needed final formatting Some budget numbers (e.g. ARRA) need finalizing

Significant mistake in isotope separator recommendation Discussion was correct

I assume this will be the basis of our discussions

July 24, 2009 Printed version available to NSAC Reformatted so page numbers have changed slightly Cover included Mistake in recommendation corrected A number of small grammar corrections but no other corrections

Executive summary including recommendations available to the public. The public should understand that the report has not yet been accepted and these are not yet NSAC’s recommendations. DOE’s Isotope Development and Production for Research and Applications Program

. Produce and sell radioactive and DOE Isotopes stable isotopes, associated

byproducts, surplus materials, and 20% 20% Other related isotope services. Commercial Research . Maintain the infrastructure required to supply isotope products and 60% related services. Medical Research . Support R&D for development and production

. Over 190 customers in FY 2008 50% 40%

. Over 560 shipments in FY 2008 30% REA CTOR STABLE 20% A CCELERA TOR

. Ten customers provided over 10% Percent of Total Shipments

85% of sales 0% FY 2006 FY 2007 FY 2008 A Change in Management was Proposed in the President’s FY09 Budget Submission

The Fiscal Year (FY) 2009 President's Request Budget proposes to transfer the Isotope Production Program from the Department of Energy (DOE) Office of Nuclear Energy to the Office of Science's Office of and rename it the Isotope Production and Applications Program. In preparation for this transfer, NSAC was requested to establish a standing committee, the NSAC Isotope (NSACI) sub-committee, to advise the DOE Office of Nuclear Physics on specific questions concerning the National Isotope Production and Applications (NIPA) Program. NSACI will be constituted for a period of two years as a subcommittee of NSAC. It will report to the DOE through NSAC who will consider its recommendations for approval and transmittal to the DOE.

The Subcommittee is asked to establish the priority of research isotope production and development, and to recommend a long-term strategic plan for the NIPA Program.

DOE has renamed it the Isotope Development and Production for Research and Applications Program FY09 Omnibus bill: DOE-ONP Budget

“Within this amount, $24,900,000 is provided for the Research Isotope Production and Applications program, and within these funds $5,000,000 is provided for the Research Isotope Development and Production Subprogram to develop and implement a research strategy consistent with the National Academy of Sciences study entitled “State of the Science of .” Consistent with the cost-sharing requirements of Public Law 101- 101, the Department is directed to develop a cost recovery strategy to ensure the long term viability of the isotope production program. The Department is directed to complete a study of the feasibility of using the University of Missouri Research Reactor to supply up to half the U. S. demand for feedstock medical imaging compounds in the form of molybdenum-99 and technetium-99.” NSACI Subcommittee

Ercan Alp Ph.D. Thomas H. Jourdan Ph.D. Argonne National Laboratory University of Central Oklahoma

Ani Aprahamian Ph.D. (co-chair) Steven M. Larson M.D. Memorial Sloan-Kettering Cancer Center Robert W. Atcher Ph.D. Richard G. Milner Ph.D. Los Alamos National Laboratory Massachusetts Institute of Technology Kelly J. Beierschmitt Ph.D. Jeffrey P. Norenberg Pharm.D. Oak Ridge National Laboratory University of New Mexico Dennis Bier M.D. Eugene J. Peterson Ph.D. Baylor College of Medicine Los Alamos National Laboratory Roy W. Brown Lee L. Riedinger Ph.D. Council on Radionuclides and Radiopharmaceuticals, Inc University of Tennessee

Daniel Decman Ph.D. Thomas J. Ruth Ph.D. Lawerence Livermore National Laboratory TRIUMF

Jack Faught Robert Tribble Ph.D. Spectra Gas Inc. Texas A&M University/ Susan Seestrom Ph.D. Donald F. Geesaman Ph.D.(co-chair) LANL – ex officio Argonne National Laboratory Roberto M. Uribe Ph.D. Kenny Jordan Kent State University Association of Energy Service Companies

A lot of people are on record saying things are not working as well as they would like

DOE-NE Expert NERAC 2005 ANS 2005 Panel 1999 SNM 2005

•Some of this is decreasing funding through 2008.

•Another component is the complexity of the mission and the current NCI 2008 NAS 2008 NAS 2007 reliance on shared resources. Current DOE Production Sites

Past and potential future participants Brookhaven – BLIP: Idaho – ATR: Richland: Ge-68 – Calibration sources for PET NP Ir-192 – Industrial non-destructive equipment; Antibody labeling Sr-90 – Y-90 gen for analysis cancer therapy Sr-82 – Rb-82 gen used in cardiac Co-60 – Sterilization of surgical imaging equipment and blood

BES Oak Ridge – HFIR: Se-75 - Industrial NDA; Protein studies Cf-252 - Industrial source W-188 - Cancer therapy Stable Isotopes Inventory: Top 10 stable isotopes sold over the last 5 years: Ca-48, Ga-69, Rb-87, Cl-37, Pt- 195, Nd-146, Sm-149, Ru-99, Zr-96 Inventory: Ac-225 - Cancer therapy Ni-63 - Explosives detection

Columbia – MURR: Los Alamos – LANSCE/IPF: Memorandum of Understanding for potential collaboration Ge-68 – Calibration sources for PET equipment; Antibody labeling Sr-82 – Rb-82 gen used in cardiac imaging Savannah River – Tritium Facility: Am-241 – Oil well logging He-3 – Neutron detection Facilities operated – Fuel source for fusion reactors NNSA/ BES By IDPRA – Lung testing IDPRA acts as sales broker FY09 Budgets Budget History in FY09$

Appropriations

Sales U-233

40000 20000 35000 18000

30000 16000

14000 25000 FY09 k$ FY09 12000 FY09 k$ 20000 10000

8000 15000 6000 10000 4000

5000 2000

0 0 2004 2005 2006 2007 2008 2009 2004 2005 2006 2007 2008 2009 Year Year Charges to NSAC

Charge 1:

As part of the NIPA Program, the FY 2009 President’s Request includes $3,090,000 for the technical development and production of critical isotopes needed by the broad U.S. community for research purposes.

NSACI is requested to consider broad community input regarding how research isotopes are used and to identify compelling research opportunities using isotopes.

The subcommittee’s response to this charge should include the identification and prioritization of the research opportunities; identification of the stable and radioactive isotopes that are needed to realize these opportunities, including estimated quantity and purity; technical options for producing each isotope; and the research and development efforts associated with the production of the isotope. Timely recommendations from NSACI will be important in order to initiate this program in FY 2009; for this reason an interim report is requested by January 31, 2009, and a final report by April 1, 2009. Charges to NSAC

Charge 2: The NIPA Program provides the facilities and capabilities for the production of research and commercial stable and radioactive isotopes, the scientific and technical staff associated with general isotope development and production, and a supply of critical isotopes to address the needs of the Nation. NSACI is requested to conduct a study of the opportunities and priorities for ensuring a robust national program in isotope production and development, and to recommend a long-term strategic plan that will provide a framework for a coordinated implementation of the NIPA Program over the next decade.

The strategic plan should articulate the scope, the current status and impact of the NIPA Program on the isotope needs of the Nation, and scientific and technical challenges of isotope production today in meeting the projected national needs. It should identify and prioritize the most compelling opportunities for the U.S. program to pursue over the next decade, and articulate their impact.

A coordinated national strategy for the use of existing and planned capabilities, both domestic and international, and the rationale and priority for new investments should be articulated under a constant level of effort budget, and then an optimal budget. To be most helpful, the plan should indicate what resources would be required, including construction of new facilities, to sustain a domestic supply of critical isotopes for the United States, and review the impacts and associated priorities if the funding available is at a constant level of effort (FY 2009 President’s Request Budget) into the out-years (FY 2009 – FY 2018). Charges to NSAC

Charge 2 Continued:

Investments in new capabilities dedicated for commercial isotope production should be considered, identified and prioritized, but should be kept separate from the strategic exercises focused on the remainder of the NIPA Program.

An important aspect of the plan should be the consideration of the robustness of current isotope production operations within the NIPA program, in terms of technical capabilities and infrastructure, research and development of production techniques of research and commercial isotopes, support for production of research isotopes, and current levels of scientific and technical staff supported by the NIPA Program. We request that you submit an interim report containing the essential components of NSACI’s recommendation to the DOE by April 1, 2009, and followed by a final report by July 31, 2009. NSACI Subcommittee Plan to meet our charges

Aug. 5-7, 2008 DOE ONP/ONE Workshop on The Nation’s Need for Isotopes: Present and Future August 8, 2008 Charge to NSAC

Nov. 13-14, 2008 Organizational meeting Publicize our charges and seek community input Dec. 15-16, 2008 Get input from government agencies Jan. 13-15, 2009 Input from customers, Ideas for production research R&D Research priorities recommendations Jan. 31, 2009 First charge interim report submitted to NSAC Feb. 10-11 2009 2- day Meeting to hear plans for facility and infrastructure improvements Mar. 2, 2009 NSAC Meeting to consider report on 1st charge Mar 25-27, 2009 3 day meeting Decide on recommendations for Long Range Plan 1 April 2009 Interim report for 2nd charge submitted by NSAC 23 April 2009 NSAC accepts report on 1st charge and transmits it to DOE

20 July 2009 Final report submitted to NSAC Federal Agencies Contacted

Air Force Office of Scientific Research, Armed Forces Radiobiology Research Institute, Department of Agriculture, Department of Defense, Department of Energy - Fusion Energy Sciences, Department of Energy- National Nuclear Security Administration - Nuclear Non-proliferation, Department of Energy-Basic Energy Sciences, Department of Energy-Biological and Environmental Research, Department of Energy-Nuclear Physics, Department of Homeland Security, Environmental Protection Agency, Federal Bureau of Investigation, National Cancer Institute, National Institute of Allergy and Infectious Disease, National Institute of Biomedical Imaging and Bioengineering, National Institute of Drug Abuse, National Institute of Environmental Health Science, National Institute of General Medical Science, National Institute of Standards and Technology, National Science Foundation - Directorate for Engineering, National Science Foundation - Directorate for Mathematical and Physical Sciences, National Science Foundation- Directorate for Biological Sciences, Office of Naval Research, State Department, U. S. Geologic Survey Professional Societies Contacted

Academy of Molecular Imaging, Academy of Radiology Imaging, Academy of Radiology Research, Amercan Association of Physicists in Medicine, American Association of Cancer Research, American Chemical Society, American Chemical Society - Division of and Technology, American College of Nuclear Physicians, American College of Radiology, American Medical Association, American Nuclear Society, American Nuclear Society - Division of Isotopes and Radiation, American Pharmacists Association - Academy of Pharmaceutical Research and Science (APhA-APRS), American Physical Society, American Physical Society - Division of Biological Physics, American Physical Society - Division of Material Physics, American Physical Society - Division of Nuclear Physics, American Society of Clinical Oncology, American Society of Hematology, American Society of Nuclear Cardiology, American Society of Theuraputic Radiation and Oncology, Council on Ionizing Radiation and Standards, Health Physics Society, National Organization of Test, Research and Training Reactors, Radiation Research Society, Radiation Therapy Oncology Group, Radiochemistry Society, Radiological Society of North America, Society of Molecular Imaging, Society of Nuclear Medicine Trade Groups contacted

Association of Energy Service Companies

Council on Radionuclides and Radiopharmaceuticals

Gamma Industry Processing Alliance

International Source Suppliers and Producers Association

Nuclear Energy Institute Written input received -January 2009 http://sun0.phy.anl.gov/pub/geesaman/Jan13-15,2009- Meeting

• American Association of Physicists in Medicine- AAPM • American Pharmacists Association-APPM-NPPS • American Physical Society- Division of Material Science • American Physical Society- Division of Nuclear Physics • American Society of Clinical Oncology • American Society for Radiation Oncology • CIRMS forwards respond to NAS study on source replacement • DOE-BES Heavy Element Chemistry • Health Physics Society • National Organization of Test, Research and Training Reactors • Nuclear Energy Institute-MURR • Society for Nuclear Medicine/Amercian College of Nuclear Physicians- SNM/ACNP NSACI Agenda: February meeting Facility Capabilities and Initiatives 10 February 11 February

8:30 Doug Wells, Idaho State University 9:00 Welcome 9:00 Donna Smith, LANL 9:15 John Pantaleo, DOE NIPA 9:40 Tracy Rudisill, SRNL 10:10 David Robertson, MURR 10:30 Richard Coats, SNL 10:50 Break 11:10 Jim Harvey, Northstar 11:10 Glen Young, ORNL 11:50 Frances Marshall, INL 11:50 Jeff Binder, ORNL 12:30 Jerry Nolen, ANL

12:30 Lunch 13:10 Lunch

14:00 Leonard Mausner, BNL 14:00-16:00 Executive Session 14:40 Brad Sherrill, NSCL/FRIB We asked the institutions to 15:20 Richard Kouzes, PNNL present their current capabilities 16:00 Break their plans. NSACI used this as 16:15 Steve Laflin, International Isotopes input and examples without 16:55 Ian Horn, NuView endorsing any individual requests. 17:35 Hugh Evans, Nuclitec ONP reviews the operation of each of the DOE facilities as it does all its program elements. First Report • Ani Aprahamian led the first report which was accepted by NSAC and transmitted to DOE on 24 April 2009 • Research Divided into – Medicine, Biology and Pharmaceuticals – Physical Sciences and Engineering – National Security and Applications • Recommendations Long Range Plan Report Outline

Charge elements Executive Summary 1. Introduction Scope, Status, 2. History of the DOE Isotopes program Impact 3. Uses A. Biology, Medicine and Pharmaceuticals Opportunities and B . Physical Sciences and Engineering impact C. Security and other Applications

4. Challenges Scope, Status, Impact 5. Stable isotope capabilities 6. Accelerator based isotope capabilities Existing and 7. Reactor Based isotope capabilities planned 8. Isotope Harvesting from long-lived capabilities stockpilies

9. R&D for production and use Robustness of 10. Trained Workforce and Education program 11, Operation of the Program

12. Budget Scenarios Optimum and CE 13. Summary budget Challenges in Radio-pharmaceuticals • Initial supply of new isotope suitable for basic characterization –R&D

• NIH wants supply to be available before funding research

• Quantities increase as clinical trials proceed. Part of the research is to establish the correct dose

• Need consistent year-round availability. In many cases, can’t stockpile

• If trials succeed, quantity needed can increase dramatically. New production techniques may be required – R&D

• If trials fail, demand can shrink dramatically.

• Risk unattractive to commercial producers Success Story – 82Sr

• 82Sr - 82Rb used in clinical positron emission tomography for cardiac perfusion studies

• Requires 70 MeV to produce

• Production and use pioneered by BNL and LANL

• Limited running time at accelerators requires multiple producers for year-round availability.

• Currently isotope with highest sales

Virtual Isotope Center Concept The Path to an Effective Program

• Communication, Communication, Communication

Isotope program has to know what to produce. - Requires forecasts from major customers and funding agencies. The NIH-DOE Working Group is an excellent example.

• Coordination with outside partners • potential unused capacity • coordinate production schedules for required availability • can introduce major complications

• R&D • create more efficient processes (R) and ones that can be shared (D)

• Transportation • make it more reliable to ship isotopes

• Skilled workforce • Make sure the ones you have are available • Ensure a new generation of isotope production workforce exists

• Make sure the facilities you have are mission ready – infrastructure and maintenance

•Where needed production capacity does not exist, new investment • Dedicated flexible accelerator with year-round availability for isotope production • New isotope separation facility Isotope Demand from NIH-DOE Working Group

Isotope Half-life Availability Comments Ac-225 10 d very limited At-211 7.2 h limited, university facility may be able to Requires  beam meet demand Bi-213 47 m requires Ac-225 Br-76 16 h not been done Low energy Br-77 2.4 d not been done Low energy Cu-64 12.7 h supply probably ok Cu-67 2.6 d NuView, more needed if large increase 70 MeV required Ho-166 1.1 d Could potentially meet demand HFIR I-124 4 d ? Low energy Lu-177 6.7 d Can be met during HFIR run cycles Weekly deliveries Pb-212 10 h Limited Commercial Re-188 17 h Limited by HFIR production cycles Th-228 1.9 y Limited - commercial From U-232 Y-86 14 h Needs can be met Low energy Zr-89 3.3 d Needs can be met Low energy

Detailed projections are made for 5 years, but these are considered sensitive In Many Cases DOE-ONP Has Already Started Down This Path

• Communication, Communication, Communication August Isotope Workshop NIH-DOE Working Group Inter-Agency Working Group on 3He Restart of 252Cf production and sales Search for a NIDC Director- new position

• Coordination with outside partners • Virtual Isotope Center

• R&D • Significant development and production for research budget line • Significant ARRA investment in research

• Make sure the facilities you have are mission ready and improve their capabilities • Significant investment in FY09 in upgrading infrastructure • Significant ARRA funding Recommendations – The Present Program

I.1: For the isotope program to be efficient and effective for the nation, it is essential that DOE-ONP maintain a continuous dialogue with all interested federal agencies and commercial isotope customers to forecast and match realistic isotope demand and achievable production capabilities. The DOE-NIH interagency working group is an excellent start for this type of communications in a critical area of isotope production and use.

I.2: We recommend devising processes for the isotope program to better communicate with users, researchers, customers, students, and the public and to seek advice from experts: ―Initiate a users group to increase communication between isotope program management and users on issues of availability, schedules, priorities, and research. ―Form expert panels as needed to give advice on issues such as definition of isotopes as research or commercial in primary usage, new production methods, and needed actions when demand exceeds supply. ―Modernize the web presence for the isotope program to give users an easier way both to learn about properties, availability, production methods, and services, and also to have access to interactive tools that help customers plan purchases and use, researchers to share information and form collaborations, and students and the general public to learn about the important uses of isotopes. Recommendations – The Present Program

I.3: Encourage the use of isotopes for research through reliable availability at affordable prices.

I.4: Coordinate production capabilities and supporting research to facilitate networking among existing DOE, commercial, and academic facilities.

I.5: Support a sustained research program in the base budget to enhance the capabilities of the isotope program in the production and supply of isotopes generated from reactors, accelerators, and separators.

I.6: Increase the robustness and agility of isotope transportation both nationally and internationally.

Important elements in this program include ―Identify and prioritize transportation needs through establishing a transportation working group. ―Initiate a collaborative effort to develop and resolve the priority issues (certification of transportation casks). Recommendations – Major Investments

II.1: Construct and operate a ~30-40 MeV variable-energy, high- current, multi-particle and supporting facilities that have the primary mission of isotope production.

The most cost-effective option to position the isotope program to ensure the continuous access to many of the isotopes required is for the program to operate a dedicated accelerator facility.

II.2: Construct and operate an electromagnetic isotope separator facility for stable and long-lived radioactive isotopes. This should include several separators for a raw feedstock through-put of about 300-600 milliAmpere (10-20 mg/hr multiplied by the atomic weight and the isotopic abundance of the isotope).

Note typo in version distributed to NSAC microAmpere→milliAmpere Why ~40 MeV variable-energy, multi-particle Accelerator?

• The priority is year-round availability of a wide variety of research isotopes. Most research isotopes can be produced at < 40 MeV • You want excellent beam properties from 15-40 MeV. This is typically hard for to do at less than ½ maximum energy • Most commercial cyclotrons have alpha energies fixed at the maximum. 211At production requires around 30 MeV. Higher energies produce too much 210At which must be minimized because its decay product binds to bone marrow. • 40 MeV allows target cooling on both sides. • Shielding and activation requirements increase significantly for 70 MeV • Production technology developed is more easily transferred to commercial producers • Only 6 isotopes require higher energy: 82Sr, 68Ge, 28Mg, 32Si, 67Cu (68Ge).

If 1) a higher energy accelerator could have excellent beam properties at 15-20 MeV, or 2) parasitic operation of the current IDPRA facitlies should not longer be available (due to termination of primary DOE missions of the host facilities) a higher energy accelerator must be considered. Why ~40 MeV variable-energy, multi-particle Accelerator?

You want 211At and not 210At Properties of a modern 70 MeV variable-energy, high-current, multi-particle Accelerator vs an existing cyclotron

U-C Davis Crocker Lab from their web site p 1.3-68 MeV 30 A

d 15-45 MeV 40 A  5-90 MeV 40 A Isotope Separators

Only electromagnetic separation currently provides the range of isotopes and enables high purity.

Scaled to capacity of 4 separators similar to Calutrons • 2 for production • 1 in set-up, maintenance or R&D • 1 dedicated to radioactive material

This gives capacity about equal to current sales.

There may be new technology, possibly classified, that may make the capacity possible with fewer devices.

There are security and export control issues with operation of high- throughput separators. This may limit the choice of available sites.

Plasma separation continues to look promising for large quantity, moderate purity applications.

There are other R&D issues to be addressed: 3He, Li Recommendations – Highly Trained Workforce

III: Invest in workforce development in a multipronged approach, reaching out to students, post-doctoral fellows, and faculty through professional training, curriculum development, and meeting/workshop participation.

The dwindling population of skilled workers in the area of isotope production and applications is a widely documented concern. • NSAC, 2004, Education in Nuclear American Chemical Society Science Division of Nuclear Chemistry and Technology • NRC, 2007, Advancing Nuclear Medicine through Innovation • AAAS, APS, CSIS, 2008, Readiness of the U. S. Nuclear Workforce for 21st Century • APS, AAAS, 2008, Nuclear Forensics: Role, State of the Art, Program Needs Budget Scenarios Table 12.1 Adjustments to 2009 President's budget request (in FY09 dollars) to implement recommendations of this report Program Element Change in Optimum Change in Constant Budget Effort Budget Stabilize Skilled Workforce +2M +1.5M Infrastructure and Maintenance +1.5M (to 3.0M) Set at 1.0M Research and Development Set at 3.0M Set at 1.2M Workforce Development +1.5M +0.3M Sales invested in infrastructure Maintain at 4% Maintain at 4% Sales invested in R&D Maintain at 2% Maintain at 2%

Capital Projects Pilot Th-229 recovery from U-233 $4M total 2011-2014 ←Recognize major New Accelerator $40M total 2011-2014 issues involved New Electromagnetic Separator $25M total 2012-2015 Future Initiative $50M total 2016-2018 ←Anticipating increased The initiatives obviously assume an aggressive schedule. future demand The initiative costs are estimates and are not based on specific proposals made to the subcommittee. There is the possibility of substantial reductions by effective use of existing resources or public-private partnerships Budget Scenarios

Proposed optimum budget in FY09 dollars

90000 U233

Advanced Concept 80000 Initiative Initiatives commissioning and infrastructure New Accelerator 70000 Electromagnetic Separator Alpha Therapy Proof of 60000 Principle Sales to operations

Sales to R&D 50000 Sales to investments

ARRA R&D

FY09 K$ FY09 40000 ARRA Operations

ARRA Infrastructure 30000 Workforce Development

Research 20000 SBIR/STTTR

Key personnel 10000 Appropriations to investment Base operations 0 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Year Budget Scenarios

Proposed constant effort budget in FY09 dollars

50000 U233 45000 Sales to operations

40000 Sales to R&D

Sales to investments 35000 ARRA R&D 30000 ARRA Operations

25000 ARRA Infrastructure FY09 K$ FY09 Workforce Development 20000 Research 15000 SBIR/STTTR

10000 Key personnel

Appropriations to 5000 investment Base operations 0 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Year Isotope Initiatives under ARRA

Research and Development on Alternative Isotope Production Technique ($4.617 Million) • Utilizes funds from stimulus funding for alternative production techniques initiatives • Dedicated to the production and development of stable and radioactive research isotopes important for the Nation • Competitive: labs and universities Enhanced Utilization for Isotope Facilities ($10 Million) • $4.425 Million is for BLIP, IPF, HFIR, INL • $5.575 Million is for investment in infrastructure at national lab facilities

Applications of Nuclear Science and Technology Initiatives ($19.4 Million + base funding) • Not specific to isotopes • Utilizes stimulus funds and base funds • Need to be NP research that is beneficial to applications • Developing technology and scientific approaches of relevance to applications is a strength of the NP program • Exploit basic nuclear science research and technological of relevance to applications • Focus on practical technologies for applications such as nuclear energy, nuclear medicine, advanced accelerator and instrumentation techniques, and nuclear security In the News - Mo-99 Health NAS report

Security Wealth NAS $200M report business

Note, at present, the isotopes program does not produce Mo-99 Issue: Mo-99/Tc-99m

Successful outcome of DOE Isotope program – Developed at BNL. Used in 70-80% of all nuclear medicine procedures ~200M$ in commercial technetium generator sales each year in US

U.S. consumption 5000-7000 6 day Curies per week (T1/2=2.75 days) From NAS study: ~60% from Canada, ~40% from Europe via Mallinckrodt Translates to ~ 1 MW of continuous fission target power Based on 7 day target irradiation, daily target removal, & 2 days for processing and shipping 7 day irradiation gives 83% of equilibrium value, 1 day of delay costs 22% of product

Issues • Reliability of Supply – old reactors are having problems • Proliferation – Most current production uses highly enriched uranium (HEU) • Was part of isotopes program portfolio in 1990’s • Currently NNSA has the responsibility, stemming from proliferation issues. • 2009 NAS report concluded LEU production is feasible and would not increase cost more than 10% • At least two commercial or public-private partnerships are seeking to solve • FY09 Omnibus language mandates a study of one of these Major concern

The supply of 99Mo, the isotope used to generate the radioactive isotope most frequently used in medical procedures, is of great concern. Recent disruptions in international supply demonstrate the vulnerability of the nation’s health care system in this area. The nation must address this vulnerability. At the present time, the isotopes program does not produce 99Mo. With the non-proliferation issues associated with the transport and use of the highly-enriched uranium currently used for 99Mo production, DOE/NNSA has the lead responsibility in this area and is actively investigating options for 99Mo commercial production. The subcommittee chose to refrain at this time from inserting itself into the intense activity underway but reiterates the importance of the issue. Summary

• The Isotope Development and Production for Research and Applications Program is a major asset for the nation’s competitiveness.

• It is an essential role for the Federal government. • unique capital investments • sensitive technology • considerable economic risk • intellectual advances

• It should focus on development and production.

• It needs to replace lost capabilities – stable isotopes – and be able to provide radioactive isotopes for research year-round.

• Following the recent significant pulse of investment, the program could operate on a constant effort budget for a few years. In the long term, this will force the nation to rely heavily on uncertain foreign sources of isotopes.

Ani and I must express our deep thanks to all the members of the subcommittee, whose wisdom, insight, and hard work created this strategic plan. Background Material FY10 Congressional Language

House Science: The Committee recommends $29.2M, $10.0M above the request, for the Isotopes Development and Production for Research and Applications, University Operations. The Committee is aware that several universities, including the University of California at Davis and Idaho State University, operate facilities with the potential to make important contributions to the nation’s supply of medical isotopes. The Committee directs the Department to work with the academic community to most cost-effectively increase the availability of medical isotopes.

NNSA: The Committee has included an additional $10M for university reactors in Office of Science Medical Isotope Production and Applications, University Operations. The Committee directs that activities to support the short term production of critical isotopes in short supply, including Mo-99, be given the highest priority for this funding. The Department should also evaluate the material processing facilities to support this effort

Senate Within the funds provided, $17.5M is for nuclear medicine medical application research. The Committee emphasizes its commitment to nuclear medicine medical application research at the DOE. All of the additional funds must be awarded competitively in one or more solicitation that includes all sources– universities, the private sector, and Government laboratories. Funding for nuclear medicine application research was previously within the BER program. Research Priorities: Medicine …

Research Activity Isotope Issue/Action Alpha therapy 225Ac Current sources are limited. One valuable source for 225Ac, 211At extraction of 229Th from 233U may soon be lost. 212Pb

Diagnostic dosimetry for proven 64Cu Used in conjunction with therapeutic agents 86Y 67Cu therapy 124I 90Y therapy 203Pb 131I therapy and immune‐diagnosis 212Pb therapy The issue is the need for a coordinated network of production facilities to provide broad availability. There is need for R&D for common target and chemical extraction procedures.

Diagnostic Tracer 89Zr Immune‐diagnosis 3.27 d half‐life allows longer temporal window for imaging of MoAbs, metabolism, bioincorporation, stemcell trafficking, etc.

Therapeutic 67Cu Requires specialized high energy production facilities and enriched targets Research Priorities: Physical Sciences

Research activity Isotope Issue/action

Begin new facility to produce and study radioactive 252Cf Supply of 252Cf is uncertain; 1 Ci source is needed each 1 ½ beams of nuclei from 252Cf fission, for research in (2.6 yr) year for at least four years. nuclear physics and astrophysics ‐ CARIBU at ANL Measure permanent atomic electric dipole moment of 225Ra Supply of 225Ra is limited. Need 10 mCi source of 225Ra every 225Ra to search for time reversal violation, proposed to (15 d) two months for at least two years be enhanced due to effects of nuclear octupole deformation; Create and understand the heaviest elements possible, 209Po, 229Th,232Th, Make certain actinides in HFIR and then prepare targets for all very short‐lived and fragile. Study the atomic physics 231Pa, 232U, accelerator‐based experiments to make superheavy and chemistry of heavy elements for basic research and 237Np,248Cm, elements; targets needed are 241Am, 249Bk, 254Es ‐ not advanced reactor concepts. 247Bk available now; need10 ‐ 100 mg on a regular basis; purity is important Neutron detectors, electric dipole moment 3He Total demand exceeds that available measurement, low temperature physics, Isotope dilution mass spectrometers 236Np, 236,244Pu, High purity 236Np is not available; others are in limited 243Am, 229Th supply; 10 ‐ 100 mg needed on a regular basis; purity is important Search for double beta decay without neutrino emission 76Ge Need to fabricate large detectors of highly enriched 76Ge; U.S. ‐ an experiment of great importance for fundamental cannot produce quantity needed, ~1000 kg symmetries Spikes for mass spectrometers 202,203,205Pb, 206Bi, 202,205Pb difficult to get in high purity in gram quantities 210Po Avogadro project ‐ worldwide weight standard based on 28Si Concern about future supply and cost of kg of material pure 28Si crystal balls needed Radioisotope micro‐power source 147Pm,244Cm Development needed for efficient conversion Isotopes for Mossbauer Spectroscopy, over 100 57Co, 119mSn Some Isotopes only available from Russia, a concern for radioactive parent/stable daughter isotopes 67Ni, 161Dy, … scientific community Charge 1: Recommendations

1. Invest in new production approaches of alpha-emitters with highest priority for 225Ac. Extraction of the thorium parent from 233U is an interim solution that needs to be seriously considered for the short term until other production capacity can become available. (Medicine #1)

2. We recommend investment in coordination of production capabilities and supporting research to facilitate networking among existing accelerators. (Medicine #2)

3. We recommend the creation of a plan and investment in production to meet these research needs for heavy elements. (Physical Sciences 1-3) Charge 1: Recommendations -continued

4. We recommend a focused study and R&D to address new or increased production of 3He. (Physical Sciences #4)

5. Research and Development efforts should be conducted to prepare for the reestablishment of a domestic source of mass-separated stable and radioactive research isotopes. (Physical Sciences 5-8 and 10)

6. We recommend that a robust investment be made into the education and training of personnel with expertise to develop new methods in the production, purification and distribution of stable and radio-active isotopes. (All) 101-101

Energy and Water Development Appropriations Act, 1990 (Engrossed as Agreed to or Passed by House) ISOTOPE PRODUCTION AND DISTRIBUTION PROGRAM FUND

For necessary expenses of activities related to the production, distribution, and sale of isotopes and related services, $16,243,000, to remain available until expended: Provided, That this amount and, notwithstanding 31 U.S.C. 3302, revenues received from the disposition of isotopes and related services shall be credited to this account to be available for carrying out these purposes without further appropriation: Provided further, That all unexpended balances of previous appropriations made for the purpose of carrying out activities related to the production, distribution, and sale of isotopes and related services may be transferred to this fund and merged with other balances in the fund and be available under the same conditions and for the same period of time: Provided further, That fees shall be set by the Secretary of Energy in such a manner as to provide full cost recovery, including administrative expenses, depreciation of equipment, accrued leave, and probable losses: Provided further, That all expenses of this activity shall be paid only from funds available in this fund: Provided further, That at any time the Secretary of Energy determines that moneys in the fund exceed the anticipated requirements of the fund, such excess shall be transferred to the general fund of the Treasury. 103-316

Energy and Water Development Appropriations Act, 1995 (Enrolled as Agreed to or Passed by Both House and Senate) DEPARTMENT OF ENERGY Energy Supply, Research and Development Activities • For expenses of the Department of Energy activities including the purchase, construction and acquisition of plant and capital equipment and other expenses incidental thereto necessary for energy supply, research and development activities, and other activities in carrying out the purposes of the Department of Energy Organization Act (42 U.S.C. 7101, et seq.), including the acquisition or condemnation of any real property or any facility or for plant or facility acquisition, construction, or expansion; purchase of passenger motor vehicles (not to exceed 25, of which 19 are for replacement only), $3,314,548,000, to remain available until expended: Provided, That the Secretary of Energy may transfer available amounts appropriated for use by the Department of Energy under title III of previously enacted Energy and Water Development Appropriations Acts into the Isotope Production and Distribution Program Fund, in order to continue isotope production and distribution activities: Provided further, That the authority to use these amounts appropriated is effective from the date of enactment of this Act: Provided further, That fees set by the Secretary for the sale of isotopes and related services shall hereafter be determined without regard to the provisions of Energy and Water Development Appropriations Act (Public Law 101 -101 ): Provided further, That amounts provided for isotope production and distribution in previous Energy and Water Development Appropriations Acts shall be treated as direct appropriations and shall be merged with funds appropriated under this head. FY09 President’s Budget Language

The Isotope Program (Isotope Production and Distribution Program Fund) produces and sells radioactive and stable isotopes, byproducts, surplus materials, and related isotope services world wide. The Isotope Program operates under a revolving fund established by the 1990 Energy and Water Appropriations Act (Public Law 101-101), as modified by Public Law 103-316. Each isotope will be priced such that the customer pays the cost of production. The DOE will continue to sell commercial isotopes at full-cost recovery.

The Program’s fiscal year appropriation will be received via transfer from the Nuclear Physics program starting in FY 2009. Prior to FY 2009, the direct appropriation was provided via transfer from the Radiological Facilities Management program within the Office of Nuclear Energy. The appropriation is used to maintain and upgrade the infrastructure that is needed to assure continued reliable production, with the production costs borne by the customers. Only funds from the Isotope Production and Application subprogram within the Nuclear Physics program will be expended on the development or production of isotopes.

There is similar language every year in the President’s request Sales revenues